FAT CELLS: Afferent and Efferent Messages Define New Approaches to Treat Obesity

Lafontan, Max

doi:10.1146/annurev.pharmtox.45.120403.095843

Cited by 160 publications

(128 citation statements)

References 193 publications

(117 reference statements)

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Other peptide hormones such as parathyroid hormone (PTH), tumor necrosis factor-alpha (TNF-␣), and interleukin-6 (IL-6) stimulate lipolysis in isolated fat cells. 33 Nevertheless, a number of questions remain about their contribution to the physiological regulation of lipid mobilization in humans.…”

Section: The Lipolytic Pathways and The Regulation Of Lipid Mobilizatmentioning

confidence: 99%

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Lafontan

Moro

Sengenès

et al. 2005

ATVB

Self Cite

View full text Add to dashboard Cite

Abstract-In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. (ATP III). The NCEP definition of the metabolic syndrome includes 3 or more of the following: abdominal obesity, defined as waist circumference Ն102 cm in men and Ͼ88 cm in women; elevated triglyceride concentration Ն150 mg/dL, low HDL cholesterol (Ͻ40 mg/dL in men and Ͻ50 mg/dL in women); elevated fasting plasma glucose level (Ն110 mg/dL); and elevated blood pressure (Ն130/85 mm Hg). 1 The presence of abdominal obesity is more closely associated with the metabolic risk factors than body mass index. The prevalence of the metabolic syndrome increases with age. Obesity interferes with many metabolic pathways which underlie numerous potential risk factors. It is very difficult to differentiate between the major and minor factors, and some remain to be discovered. 2 This complexity leaves the area open and challenges basic and clinical researchers to uncover novel metabolic pathways. The discovery that cardiac natriuretic peptides (NPs) control human fat cell function is a provocative observation which reveals an unsuspected link between heart and adipose tissue. NPs exert potent lipolytic effects (eg, stimulation of hydrolysis of triacylglycerols stored in adipocytes) in isolated human fat cells. 3 When administered intravenously, they potently increase plasma glycerol and nonesterified fatty acid (NEFA) levels; in other words they stimulate lipid mobilization. 4 Before the discovery of the NP pathway, catecholamines and insulin were considered to be the major acute regulators of lipid mobilization in humans: they both act through a cAMP-dependent regulation of lipolysis. In contrast, NPs activate a 3Ј, 5Ј-cyclic guanosine monophosphate (cGMP)-dependent pathway that is completely independent from the cAMP-dependent pathway. 5 The NPs may represent a promising new pathway contributing to the control of lipid mobilization in humans in physiological and pathological conditions. The introductory section

show abstract

Section: The Lipolytic Pathways and The Regulation Of Lipid Mobilizatmentioning

confidence: 99%

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Lafontan

Moro

Sengenès

et al. 2005

ATVB

Self Cite

View full text Add to dashboard Cite

show abstract

“…Well-known examples of signalling molecules (adipokines) secreted by adipose tissue are leptin, adiponectin, resistin and IL-6 [2]. Adipokine secretion is responsive to afferent messages to the fat cells [3]. Under conditions of insulin resistance and type 2 diabetes, fat cells are subjected to increased levels of insulin, which may have a major impact on the adipokines.…”

Section: Introductionmentioning

confidence: 99%

Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing

Wang

Keijer²,

Bunschoten³

et al. 2006

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Under conditions of insulin resistance and type 2 diabetes, fat cells are subjected to increased levels of insulin, which may have a major impact on the secretion of adipokines. Materials and methods Using transcriptomics and proteomics, we investigated how insulin affects the transcription and protein secretion profile of mature 3T3-L1 adipocytes. Results We found that insulin has a significant impact on protein secretion of 3T3-L1 adipocytes. However, transcription is not the major regulation point for these secreted proteins. For extracellular matrix components, our data suggest that the mRNA level of processing enzymes, but not of target proteins, is the regulating point at which insulin stimulates secretion and function of the relevant proteins. Among these enzymes, we report a novel finding, namely that sulfatase 2 gene is regulated by insulin, which may induce a functional change in cultured adipocytes. Conclusions/interpretation We propose that enhancement of protein processing and secretion rather than transcription of the secreted protein genes is part of the strategic role of insulin in the induction of cellular responses.

show abstract

“…Part of this association may be explained by adipose tissue products that exert autocrine, paracrine and/ or endocrine effects that may affect metabolism. [1][2][3] A functional renin-angiotensin system (RAS) is present in human adipose tissue, [4][5][6] and local generation of angiotensin II (Ang II), the effector molecule of the RAS, by human (pre)adipocytes has been demonstrated. 7 The adipose tissue RAS may be involved in obesity-related disorders, such as insulin resistance, 8,9 possibly through an effect on adipocyte differentiation.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II: a hormone that affects lipid metabolism in adipose tissue

et al. 2006

View full text Add to dashboard Cite

Background: Alterations in adipose tissue lipolysis may contribute to the pathophysiology of obesity and insulin resistance. We examined the effects of angiotensin II (Ang II) on abdominal subcutaneous adipose tissue lipolysis in humans. Methods and results: First, adipocytes obtained from nine normal weight and seven obese subjects were stimulated with Ang II (10 À14 -10 À6 M). Glycerol concentration in the medium, used as an indicator of adipocyte lipolysis, was significantly reduced (B20%) after Ang II stimulation in adipocytes from normal weight (P ¼ 0.04) and obese subjects (Po0.001). Based on these observations, adipocytes of seven additional obese subjects were stimulated with lower doses of Ang II (10 À17 -10 À6 M) in the presence and absence of Ang II type 1 (AT 1 ) receptor blockade. Lipolysis was dose dependently inhibited by B20 to 25% after Ang II stimulation (P ¼ 0.001). AT 1 receptor blockade completely abolished the Ang II-induced effects (P ¼ 0.35). Conclusion: Ang II directly inhibits abdominal subcutaneous adipocyte lipolysis in normal weight and obese subjects via the AT 1 receptor.

show abstract

FAT CELLS: Afferent and Efferent Messages Define New Approaches to Treat Obesity

Cited by 160 publications

References 193 publications

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing

Angiotensin II: a hormone that affects lipid metabolism in adipose tissue

Contact Info

Product

Resources

About